2m8r

Pre-Fusion Solution NMR Structure of Neuronal SNARE Syntaxin 1APre-Fusion Solution NMR Structure of Neuronal SNARE Syntaxin 1A

Structural highlights 2m8r is a 1 chain structure with sequence from Rattus norvegicus. The November 2013 RCSB PDB Molecule of the Month feature on SNARE Proteins by David Goodsell is 10.2210/rcsb_pdb/mom_2013_11. Full experimental information is available from OCA. For a guided tour on the structure components use FirstGlance. Resources: FirstGlance, OCA, PDBe, RCSB, PDBsum, ProSAT Function STX1A_RAT Potentially involved in docking of synaptic vesicles at presynaptic active zones. May play a critical role in neurotransmitter exocytosis. May mediate Ca(2+)-regulation of exocytosis acrosomal reaction in sperm. Publication Abstract from PubMed The assembly of the three neuronal soluble N-ethylmaleimide-sensitive factor attachment protein (SNAP) receptor (SNARE) proteins synaptobrevin 2, syntaxin-1A, and SNAP-25 is the key step that leads to exocytotic fusion of synaptic vesicles. In the fully assembled SNARE complex, these three proteins form a coiled-coil four-helix bundle structure by interaction of their respective SNARE motifs. Although biochemical and mutational analyses strongly suggest that the heptad-repeat SNARE motifs zipper into the final structure, little is known about the prefusion state of individual membrane-bound SNAREs and how they change conformation from the unzippered prefusion to the zippered postfusion state in a membrane environment. We have solved the solution NMR structure of micelle-bound syntaxin-1A in its prefusion conformation. In addition to the transmembrane helix, the SNARE motif consists of two well-ordered, membrane-bound helices separated by the "0-layer" residue Gln226. This unexpected structural order of the N- and C-terminal halves of the uncomplexed SNARE motif suggests the formation of partially zippered SNARE complex intermediates, with the 0-layer serving as a proofreading site for correct SNARE assembly. Interferometric fluorescence measurements in lipid bilayers confirm that the open SNARE motif helices of syntaxin interact with lipid bilayers and that association with the other target-membrane SNARE SNAP-25 lifts the SNARE motif off the membrane as a critical prerequisite for SNARE complex assembly and membrane fusion. Prefusion structure of syntaxin-1A suggests pathway for folding into neuronal trans-SNARE complex fusion intermediate.,Liang B, Kiessling V, Tamm LK Proc Natl Acad Sci U S A. 2013 Nov 11. PMID:24218570 From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. See Also Syntaxin 3D structures

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